Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Regulation of the Fusion of Mononuclear Osteoclasts Into Bone-Resorbing Osteoclasts by GM-CSF Via RAS/ERK Pathway

Lee1,  Eun Gyeong, Yun1,  Hee Jin, Hong1,  Yun Kyung, Lee2,  Myung Soo, Lee3,  Sang-IL, Kim4,  Hyun-Ok, Hwang5,  Min Ho

Chonbuk National University Medical School and Research Institute of Clinical Medicine. Jeonju, South Korea
Wonkwang university hospital, Iksan, South Korea
College of Medicine, Gyeongsang National University, Jinju, South Korea
Gyongsang University, Jinju, South Korea
Presbyterian medical center, Jeonju, South Korea
Pusan National University Mediacal School, Busan, South Korea

Purpose:

GM-CSF has been shown to suppress RANKL-mediated osteoclast differentiation by inhibiting c-Fos. However, GM-CSF plays a critical role in osteoclast-mediated bone destruction under certain pathologic conditions including rheumatoid arthritis. Thus, this study was performed to define the role of GM-CSF in fusion of mononuclear osteoclasts for osteoclast differentiation and bone resorption.

Methods:

Prefusion osteoclasts (pOCs) were generated from bone marrow macrophages treated with M-CSF and RANKL. pOCs were cultured to investigate the effect of GM-CSF on multinuclear cell formation. Expression of c-Fos, NFATc1, and DC-STAMP were determined by RT-PCR and Immunoblotting. We used constitutively active (CA)-MEK adenovirus to examine the phosphorylation of ERK induced by GM-CSF.

Results:

GM-CSF enhanced the fusion of pOCs for osteoclastogenesis. GM-CSF-stimulated pOCs had intact actin ring and could resorb bone. GM-CSF induced the expression of DC-STAMP, which was mediated by inducing NFATc1 via induction of c-Fos. The expression of c-Fos and NFATc1 was regulated by ERK pathway. In addition, pOCs infected with constitutively active (CA)-MEK adenovirus expressed c-Fos and NFATc1. The ectopic expression of CA-MEK induced NFATc1 binding to the DC-STAMP promoter and promoted the expression of DC-STAMP. CA-MEK-infected pOCs undergo cell-cell fusion and resorb bone.

Conclusion:

GM-CSF can induce the fusion of pOCs into multinucleated osteoclasts by inducing the expression of DC-STAMP and thus involve in osteoclast differentiation. GM-CSF-stimulated pOCs have a typical actin ring structure and can induce bone resorption.

To cite this abstract, please use the following information:
Lee, Eun Gyeong, Yun, Hee Jin, Hong, Yun Kyung, Lee, Myung Soo, Lee, Sang-IL, Kim, Hyun-Ok, et al; Regulation of the Fusion of Mononuclear Osteoclasts Into Bone-Resorbing Osteoclasts by GM-CSF Via RAS/ERK Pathway [abstract]. Arthritis Rheum 2009;60 Suppl 10 :28
DOI: 10.1002/art.25111

Abstract Supplement

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